Process for preparing substituted chroman derivatives

ABSTRACT

The invention relates to a process for preparing substituted chroman derivatives of the general formula VII, ##STR1## where X is the group --CN, --COOR 3 , --CHO, --CH 2  OR 7  or --CH(OR 8 ) 2 , 
     R 2  is a C 1  -C 23  -alkyl, C 2  -C 23  -alkenyl, C 6  -C 18  -aryl or C 7  -C 18  -aralkyl radical, 
     R 3  is hydrogen or an optionally substituted C 1  -C 4  -alkyl radical, 
     R 4 , R 5 , R 6  are, independently of one another, hydrogen or a C 1  -C 4  -alkyl radical, 
     R 7  is hydrogen or a C 1  -C 4  -alkyl radical, 
     R 8  is a C 1  -C 4  -alkyl radical, or the two radicals are a C 2  -C 6  -alkylene radical which links the two oxygen atoms to form a cyclic acetal and is optionally branched or may carry one or two carboxyl groups, cyclohexyl or phenyl radicals, 
     and to the novel intermediates of the process.

The invention relates to a process for preparing substituted chromanderivatives of the general formula VII, ##STR2## where X is the group--CN, --COOR³, --CHO, --CH₂ OR⁷ or --CH(OR⁸)₂,

R² is a C₁ -C₂₃ -alkyl, C₂ -C₂₃ -alkenyl, C₆ -C₁₈ -aryl or C₇ -C₁₈-aralkyl radical,

R³ is hydrogen, a C₁ -C₄ -alkyl radical, a C₁ -C₄ -haloalkyl radical, aC₁ -C₄ -hydroxyalkyl radical or a C₁ -C₄ -aminoalkyl radical,

R⁴, R⁵, R⁶ are, independently of one another, hydrogen or a C₁ -C₄-alkyl radical,

R⁷ is hydrogen or a C₁ -C₄ -alkyl radical,

R⁸ is a C₁ -C₄ -alkyl radical, or the two radicals are a C₂ -C₆-alkylene radical which links the two oxygen atoms to form a cyclicacetal and is optionally branched or may carry one or two carboxylgroups, cyclohexyl or phenyl radicals,

and to the novel intermediates for the process.

The substituted chroman derivatives of the general formula VII are knownintermediates in demand for pharmaceutical agents and vitamins (e.g.tocopherol). Starting from 6-acetyloxychroman-2-aldehyde it has beenpossible to prepare, inter alia, α-tocopherol by a Wittig reaction witha phosphonium salt (T. Netscher, Chimia 1996, 50, 563-567; H. Mayer, P.Schudel, R. Ruegg, O. Isler, Helv. Chim. Acta 1963, 46, 650). Inaddition, these compounds, e.g. the 6-hydroxychroman-2-carboxylic acids,themselves have an antioxidant effect in animal fat, vegetable oils andemulsions (J. W. Scott et al., J. of the American Oil Chemists Society,1974, 51, 200-203).

The preparation of substituted chroman derivatives by condensation ofthe corresponding hydroquinones with allyl alcohols has been disclosed(U.S. Pat. No 2,411,969, WO 9821197 A2).

In addition, DE 2364141 A1 describes a similar approach by reaction of ahydroquinone with unsaturated ketones or acetals in the presence of anacid.

It is common to all the processes described to date that the aromaticsystem is employed as synthon and the pyran moiety is subsequently builton by electrophilic aromatic substitution.

These reactions have the disadvantage that chromans unsubstituted in thearomatic system are difficult to prepare because these electron-richaromatic systems are prone to multiple alkylation.

Moreover, with different alkyl groups on the aromatic system,regioselectivity problems arise in the abovementioned syntheses, i.e. itis not possible to prepare all desired substitution patterns on thearomatic moiety in the chroman structure equally satisfactorily.

It is an object of the present invention to develop a process forpreparing the chroman derivatives which is more flexible in terms of thesubstituents, is economical and proceeds via easily handledintermediates and reagents.

We have found that this object is achieved in that the chromanderivatives of the general formula VII mentioned at the outset can beprepared by a multistage process, which comprises, in a first step,reacting substituted acroleins of the general formula I, ##STR3## whereR¹ is a C₁ -C₄ -alkyl, C₆ -C₁₈ -aryl, C₇ -C₁₈ -aralkyl, C₁ -C₄ -acyl, ahalogenated C₁ -C₄ -acyl radical or another acid-labile protective groupfor the hydroxyl group,

with acrylonitriles, acrylates, acroleins, acrolein acetals, allylalcohols or allyl ethers of the general formula II ##STR4## to give thecorresponding 3,4-dihydro-2H-pyrans of the general formula III ##STR5##and, in a second step, reacting the latter with an acid to give thecorresponding 5-oxotetrahydropyrans of the general formula IV ##STR6##and, in a third step, reacting the latter with substituted vinyl ketonesof the general formula V ##STR7## to give the correspondingchromen-6-one derivatives of the general formula VI ##STR8## and, in a4th step, dehydrogenating the latter to give the substituted chromanderivatives of the general formula VII.

The starting materials for the process are substituted acroleins of thegeneral formula I and acrylonitriles, acrylates, acroleins, acroleinacetals, allyl alcohols or allyl ethers of the general formula II.

The substituted acroleins of the general formula I in the first step ofthe process according to the invention are the diene component in ahetero-Diels-Alder reaction.

The R¹ radical in the substituted acroleins can be a C₁ -C₄ -alkyl, C₆-C₁₈ -aryl, C₇ -C₁₈ -aralkyl, an optionally halogenated C₁ -C₄ -acylradical or another acid-labile protective group for the hydroxyl group.A C₁ -C₄ -alkyl radical means a methyl, ethyl, n-propyl, i-propyl,n-butyl, i-butyl or t-butyl radical, with methyl being preferred.Examples of C₆ -C₁₈ -aryl radicals are phenyl, naphthyl or phenyl whichis optionally substituted one to three times by C₁ -C₄ -alkyl radicals.C₇ -C₁₈ -Aralkyl radicals mean radicals such as benzyl or phenylethyl.

Examples of C₁ -C₄ -acyl radicals or halogenated C₁ -C₄ -acyl radicals,i.e. those substituted by one to three identical or different halogenradicals such as Cl, Br, I or F, are acetyl, monochloro-, dichloro- ortrichloroacetyl, trifluoroacetyl, propionyl or butyryl.

R¹ can also be another acid-labile protective group for the hydroxylgroup of the enol. It is possible in principle to use any acid-labileprotective group. Preferred acid-labile protective groups are theacid-labile protective groups for hydroxyl groups disclosed in theliterature (T. W. Greene, Protective Groups in Organic Synthesis, JohnWiley & Sons New York, 1981, pages 14-71; P. J. Kocienski, ProtectingGroups, Georg Thieme Verlag Stuttgart, 1994, pages 21-94). Particularlypreferred acid-labile protective groups are

esters such as

phenylacetates, triphenylmethoxyacetate, phenoxyacetates,halophenoxyacetates, haloalkylphenoxyacetates, formate, benzoylformate,3-phenylpropionate, isobutyrate, pivaloate, adamantoate, crotonates orbenzoates;

or

aliphatic and aromatic ethers such as methyl, benzyl, o-nitrobenzyl,p-methoxybenzyl, 3,4-dimethoxybenzyl ethers, trityls,p-methoxyphenyl(diphenyl)methyl, 4,4', 4"-tris(benzoyloxy)trityl,di(p-methoxyphenyl)phenylmethyl, tert-butyls, 9-phenyl-9-xanthenyl,allyls, 2-(trimethylsilyl)ethyl.

Preferred substituted acroleins of the general formula I areα-methoxyacrolein, α-benzyloxyacrolein or acetoxyacrolein.

The substituted acrylonitriles (X=--CN), acroleins (X=--CHO), acrylates(X=--COOR³), acrolein acetals (X=--CH(OR⁸)₂), allyl ethers (X=--CH₂ OR⁷)or allyl alcohols (X=--CH₂ OR⁷ ; R⁷ =hydrogen) of the general formula IIin the first step of the process according to the invention are the enecomponent in a hetero-Diels-Alder reaction.

The R² radical can be a C₁ -C₂₃ -alkyl radical such as methyl, ethyl,n-propyl, i-propyl, n-Butyl, i-butyl, t-butyl, pentyl, hexyl, heptyl,octyl, nonyl or 4,8,12-trimethyltridecyl, in particular methyl, a C₂-C₂₃ -alkenyl radical such as ethenyl(vinyl), propenyl (allyl),4-methyl-3-pentenyl, 4,8-dimethyl-3,7-nonadienyl or4,8,12-trimethyl-3,7,11-tridecatrienyl, a C₆ -C₁₈ -aryl radical asmentioned above for R¹, in particular phenyl, or a C₇ -C₁₈ -aralkylradical as mentioned above for R¹, in particular benzyl.

Preferred R² -substituted acrylonitriles (X=--CN) of the formula II are2-methylacrylonitrile, 2-(4,8,12-trimethyltridecyl)-acrylonitrile,2-(4-methyl-3-pentenyl)acrylonitrile,2-(4,8-dimethyl-3,7-nonadienyl)acrylonitrile or2-(4,8,12-trimethyl-3,7,11-tridecatrienyl)acrylonitrile.

Preferred R² -substituted acroleins (X=--CHO) of the formula II are2-methylacrolein (methacrolein), 2-(4,8,12-trimethyl-tridecyl)acrolein,2-(4-methyl-3-pentenyl)acrolein, 2-(4,8-dimethyl-3,7-nonadienyl)acroleinor 2-(4,8,12-trimethyl-3,7,11-tridecatrienyl)acrolein.

R² -substituted acrylates (X=--COOR³) mean substituted acrylic acids (R³=hydrogen) or acrylic esters (R³ =a C₁ -C₄ -alkyl radical, a C₁ -C₄-haloalkyl radical, a C₁ -C₄ -hydroxyalkyl radical or a C₁ -C₄-aminoalkyl radical).

C₁ -C₄ -Alkyl radicals for R³ mean the C₁ -C₄ -alkyl radicals mentionedabove for R¹, in particular methyl or ethyl.

C₁ -C₄ -Haloalkyl radicals mean C₁ -C₄ -alkyl radicals substituted byone to three identical or different halogen radicals such as F, Cl, Bror I. Examples of C₁ -C₄ -haloalkyl radicals are 2-chloroethyl,1,2-dichloroethyl or 2,2,2-trichloroethyl and the correspondingbromoethyl radicals.

C₁ -C₄ -Hydroxyalkyl radicals mean C₁ -C₄ -alkyl radicals substituted byone to three hydroxyl groups. Examples of C₁ -C₄ -hydroxyalkyl radicalsare 2-hydroxyethyl or 1,2-dihydroxyethyl.

C₁ -C₄ -Aminoalkyl radicals mean C₁ -C₄ -alkyl radicals substituted byone to three amino groups. Amino groups mean NH₂ groups, mono(C₁ -C₄-)alkylamino groups or di(C₁ -C₄ -)alkylamino groups. Examples of C₁ -C₄-aminoalkyl radicals are aminoethyl, 2-methylaminoethyl,2-dimethylaminoethyl or ethylmethylaminoethyl.

Preferred substituted acrylates of the general formula II are2-methylacrylic acid (methacrylic acid), methyl methacrylate, ethylmethacrylate, 2-hydroxyethyl methacrylate, 2-chloroethyl methacrylate,2-dimethylaminoethyl methacrylate, 2-(4,8,12-trimethyltridecyl)acrylicacid, 2-(4-methyl-3-pentenyl)-acrylic acid,2-(4,8-dimethyl-3,7-nonadienyl)acrylic acid,2-(4,8,12-trimethyl-3,7,11-tridecatrienyl)acrylic acid, methyl2-(4,8,12-trimethyltridecyl)acrylate, methyl2-(4-methyl-3-pentenyl)acrylate, methyl2-(4,8-dimethyl-3,7-nonadienyl)acrylate, methyl2-(4,8,12-trimethyl-3,7,11-tridecatrienyl)acrylate, ethyl2-(4,8,12-trimethyltridecyl)acrylate, ethyl2-(4-methyl-3-pentenyl)acrylate, ethyl2-(4,8-dimethyl-3,7-nonadienyl)acrylate, ethyl2-(4,8,12-trimethyl-3,7,11-tridecatrienyl)acrylate, 2-hydroxyethyl2-(4,8,12-trimethyltridecyl)acrylate, 2-hydroxyethyl2-(4-methyl-3-pentenyl)acrylate, 2-hydroxyethyl2-(4,8-dimethyl-3,7-nonadienyl)acrylate, 2-hydroxyethyl2-(4,8,12-trimethyl-3,7,11-tridecatrienyl)acrylate, 2-chloroethyl2-(4,8,12-trimethyltridecyl)acrylate, 2-chloroethyl)2-(4-methyl-3-pentenyl)acrylate, 2-chloroethyl2-(4,8-dimethyl-3,7-nonadienyl)acrylate or 2-chloroethyl2-(4,8,12-trimethyl-3,7,11-tridecatrienyl)acrylate, 2-dimethylaminoethyl 2-(4,8,12-trimethyltridecyl)acrylate, 2-dimethylaminoethyl2-(4-methyl-3-pentenyl)acrylate, 2-dimethylaminoethyl2-(4,8-dimethyl-3,7-nonadienyl)acrylate or 2-dimethylaminoethyl2-(4,8,12-trimethyl-3,7,11-tridecatrienyl)- acrylate.

In the case of the R² -substituted allyl ethers (X=--CH₂ OR⁷) or allylalcohols (X=--CH₂ OR⁷ ; R⁷ =hydrogen), R⁷ can be hydrogen or a C₁ -C₄-alkyl radical as described above for R¹, in particular methyl or ethyl.

Preferred substituted allyl ethers of the general formula II are2-methyl-3-methoxypropene, 2-methyl-3-ethoxypropene,2-(4,8,12-trimethyltridecyl)-3-methoxypropene,2-(4-methyl-3-pentenyl)-3-methoxypropene,2-(4,8-dimethyl-3,7-nonadienyl)-3-methoxypropene,2-(4,8,12-trimethyl-3,7,11-tridecatrienyl)-3-methoxypropene,2-(4,8,12-trimethyltridecyl)-3-ethoxypropene,2-(4-methyl-3-pentenyl)-3-ethoxypropene,2-(4,8-dimethyl-3,7-nonadienyl)-3-ethoxypropene or2-(4,8,12-trimethyl-3,7,11-tridecatrienyl)-3-ethoxypropene.

Preferred substituted allyl alcohols of the general formula II are2-methyl-2-propen-1-ol (2-methylallyl alcohol, methallyl alcohol),2-(4,8,12-trimethyltridecyl)-2-propen-1-ol,2-(4-methyl-3-pentenyl)-2-propen-1-ol,2-(4,8-dimethyl-3,7-nonadienyl)-2-propen-1-ol or2-(4,8,12-trimethyl-3,7,11-trideca-trienyl)-2-propen-1-ol.

In the case of the R² -substituted acrolein acetals (X=--CH (OR⁸)₂), R⁸is a C₁ -C₄ -alkyl radical as described above for R¹, in particularmethyl, or the two R⁸ radicals are a C₂ -C₆ -alkylene radical whichlinks the two oxygen atoms to form a cyclic acetal and is optionallybranched or carries up to two carboxyl groups, cyclohexyl or phenylradicals. Preferred C₂ -C₆ -alkylene radicals are ethylene, propylene,butylene or neopentylene. Preferred C₂ -C₆ -alkylene radicals carryingup to two carboxyl groups, cyclohexyl or phenyl radicals are ethyleneradicals substituted in position 1 and/or 2 by said radicals.Symmetrically substituted C₂ linkers are preferably those listed below,where the linkage points are indicated by a line showing thestereochemistry: ##STR9##

Preferred substituted acrolein acetals of the general formula II areaccordingly 2-methyl-3,3-dimethoxypropene, 2-methyl-3,3-diethoxypropene,2-methyl-3,3-dipropoxypropene, 2-methyl-3,3-dibutoxypropene,2-(4,8,12-trimethyltridecyl)-3,3-dimethoxypropene,2-(4,8,12-trimethyltridecyl)-3,3-diethoxypropene,2-(4,8,12-trimethyltridecyl)-3,3-dipropoxypropene,2-(4,8,12-trimethyltridecyl)-3,3-dibutoxypropene,2-(4,8,12-trimethyltridecyl)-3,3-dimethoxypropene,2-(4,8,12-trimethyltridecyl)-3,3-diethoxypropene,2-(4,8,12-trimethyltridecyl)-3,3-dipropoxypropene,2-(4,8,12-trimethyltridecyl)-3,3-dibutoxypropene,2-(4-methyl-3-pentenyl)-3,3-dimethoxypropene,2-(4-methyl-3-pentenyl)-3,3-diethoxypropene,2-(4-methyl-3-pentenyl)-3,3-dipropoxypropene,2-(4-methyl-3-pentenyl)-3,3-dibutoxypropene,2-(4,8-dimethyl-3,7-nonadienyl)-3,3-dimethoxypropene,2-(4,8-dimethyl-3,7-nonadienyl)-3,3-diethoxypropene,2-(4,8-dimethyl-3,7-nonadienyl)-3,3-dipropoxypropene,2-(4,8-dimethyl-3,7-nonadienyl)-3,3-dibutoxypropene,2-(4,8,12-trimethyl-3,7,11-tridecatrienyl)-3,3-dimethoxypropene,2-(4,8,12-trimethyl-3,7,11-tridecatrienyl)-3,3-diethoxypropene,2-(4,8,12-trimethyl-3,7,11-tridecatrienyl)-3,3-dipropoxypropene,2-(4,8,12-trimethyl-3,7,11-tridecatrienyl)-3,3-dibutoxypropene,2-(1-methylvinyl)-4,5-dimethyl[1,3]dioxane,2-(1-(4,8,12-trimethyltridecyl)vinyl)-4,5-dimethyl[1,3]dioxane,2-(1-(4-methyl-3-pentenyl)vinyl)-4,5-dimethyl[1,3]dioxane,2-(1-(4,8-dimethyl-3,7-nonadienyl)vinyl)-4,5-dimethyl[1,3]-dioxane,2-(1-(4,8,12-trimethyl-3,7,11-tridecatrienyl)vinyl)-4,5-dimethyl[1,3]dioxane,2-(1-methylvinyl)-4,5-dicyclohexyl-[1,3]-dioxolane,2-(1-(4,8,12-trimethyltridecyl)vinyl)-4,5-dicyclo-hexyl[1,3]dioxolane,2-(1-(4-methyl-3-pentenyl)vinyl)-4,5-dicyclohexyl-[1,3]dioxolane,2-(1-(4,8-dimethyl-3,7-nonadienyl)vinyl)-4,5-dicyclohexyl-[1,3]-dioxolane,2-(1-(4,8,12-trimethyl-3,7,11-tridecatrienyl)vinyl)-4,5-dicyclo-hexyl-[1,3]dioxolane,2-(1-methylvinyl)-[4R,5R]-4,5-dicyclohexyl-[1,3]dioxolane,2-(1-(4,8,12-trimethyltridecyl)vinyl)-[4R,5R]-4,5-dicyclohexyl-[1,3]dioxolane,2-(1-(4-methyl-3-pentenyl)-vinyl)-[4R,5R]-4,5-dicyclohexyl-[1,3]dioxolane,2-(1-(4,8-dimethyl-3,7-nonadienyl)vinyl)-[4R,5R]-4,5-dicyclo-hexyl-[1,3]dioxolane,2-(1-(4,8,12-trimethyl-3,7,11-tridecatrienyl)vinyl)-[4R,5R]-4,5-dicyclohexyl-[1,3]dioxolane,2-(1-methylvinyl)-[4S,5S]-4,5-dicyclohexyl-[1,3]dioxolane,2-(1-(4,8,12-trimethyltridecyl)vinyl)-[4S,5S]-4,5-dicyclohexyl-[1,3]dioxolane,2-(1-(4-methyl-3-pentenyl)vinyl)-[4S,5S]-4,5-dicyclohexyl-[1,3]dioxolane,2-(1-(4,8-dimethyl-3,7-nonadienyl)vinyl)-4,5-dicyclohexyl-[1,3]dioxolane,2-(1-(4,8,12-trimethyl-3,7,11-tridecatrienyl)vinyl)-[4S,5S]-4,5-dicyclohexyl-[1,3]dioxolane,2-(1-methylvinyl)-4,5-diphenyl-[1,3]dioxolane,2-(1-(4,8,12-trimethyltridecyl)vinyl)-4,5-diphenyl-[1,3]dioxolane,2-(1-(4-methyl-3-pentenyl)vinyl)-4,5-diphenyl-[1,3]dioxolane,2-(1-(4,8-dimethyl-3,7-nonadienyl)-vinyl)-4,5-diphenyl-[1,3]dioxolane,2-(1-(4,8,12-trimethyl-3,7,11-tridecatrienyl)vinyl)-4,5-diphenyl-[1,3]-dioxolane,2-(1-methylvinyl)-[4R,5R]-4,5-diphenyl-[1,3]dioxolane,2-(1-(4,8,12-trimethyltridecyl)vinyl)-[4R,5R]-4,5-diphenyl-[1,3]-dioxolane,2-(1-(4-methyl-3-pentenyl)vinyl)-[4R,5R]-4,5-diphenyl-[1,3]dioxolane,2-(1-(4,8-dimethyl-3,7-nonadienyl)-vinyl)-[4R,5R]-4,5-diphenyl-[1,3]dioxolane,2-(1-(4,8,12-trimethyl-3,7,11-tridecatrienyl)vinyl)-[4R,5R]-4,5-diphenyl-[1,3]dioxolane,2-(1-methylvinyl)-[4S,5S]-4,5-diphenyl-[1,3]dioxolane,2-(1-(4,8,12-trimethyltridecyl)vinyl)-[4S,5S]-4,5-diphenyl-[1,3]dioxolane,2-(1-(4-methyl-3-pentenyl)vinyl)-[4S,5S]-4,5-diphenyl-[1,3]dioxolane,2-(1-(4,8-dimethyl-3,7-nonadienyl)vinyl)-4,5-diphenyl-[1,3]dioxolane,2-(1-(4,8,12-trimethyl-3,7,11-tridecatrienyl)vinyl)-[4S,5S]-4,5-diphenyl-[1,3]dioxolane,2-(1-methylvinyl)-[1,3]dioxolane-4,5-dicarboxylic acid,2-(1-(4,8,12-trimethyltridecyl)vinyl)-[1,3]dioxolane-4,5-dicarboxylicacid, 2-(1-(4-methyl-3-pentenyl)-vinyl)- [1,3]dioxolane-4,5-dicarboxylicacid,2-(1-(4,8-dimethyl-3,7-nonadienyl)vinyl)-[1,3]dioxolane-4,5-dicarboxylicacid,2-(1-(4,8,12-trimethyl-3,7,11-tridecatrienyl)vinyl)-[1,3]-dioxolane-4,5-dicarboxylicacid, 2-(1-methylvinyl)- [1,3]-dioxolane-[4R,5R]-4,5-dicarboxylic acid,2-(1-(4,8,12-trimethyltridecyl)vinyl)-[1,3]dioxolane-[4R,5R]-4,5-dicarboxylicacid, 2-(1-(4-methyl-3-pentenyl)vinyl)-[1,3]-dioxolane-[4R,5R]-4,5-dicarboxylic acid,2-(1-(4,8-dimethyl-3,7-nonadienyl)vinyl)-[1,3]dioxolane-[4R,5R]-4,5-dicarboxylicacid,2-(1-(4,8,12-trimethyl-3,7,11-tridecatrienyl)vinyl)-[1,3]-dioxolane-[4R,5R]-4,5-dicarboxylicacid, 2-(1-methylvinyl)-[1,3]dioxolane-[4S,5S]-4,5-dicarboxylic acid,2-(1-(4,8,12-trimethyltridecyl)vinyl)-[1,3]dioxolane-[4S,5S]-4,5-dicarboxylicacid,2-(1-(4-methyl-3-pentenyl)vinyl)-[1,3]-dioxolane-[4S,5S]-4,5-dicarboxylicacid,2-(1-(4,8-dimethyl-3,7-nonadienyl)vinyl)-[1,3]dioxolane-[4S,5S]-4,5-dicarboxylicacid or2-(1-(4,8,12-trimethyl-3,7,11-tridecatrienyl)vinyl)-[1,3]dioxolane-[4S,5S]-4,5-dicarboxylicacid.

In the first step of the process according to the invention, the dienecomponent of the general formula I is reacted with the ene component ofthe general formula II in a 4+2 cycloaddition (hetero-Diels-Alderreaction).

Hetero-Diels-Alder reactions of electron-poor ene components such asacrylates, acroleins, allyl alcohols or crotonates with acrolein oracroleins alkylated at position 1 or 2 are known.

Thus, it is known that equimolar amounts of methyl vinyl ketone andmethyl methacrylate can be converted under (hetero-)Diels-Alderconditions (200° C., 2h) into the mixed Diels-Alder product(2-(carboxymethyl)-2,6-dimethyl-3,4-dihydro-2H-pyran) and the methylvinyl ketone dimer in the ratio 1:1 (B. P. Mundy, R. D. Otzenberger, A.R. DeBernadis, J. Org. Chem., 36, 1971, p. 2390). More recentinvestigations confirm this result (J. G. Jun, D. W. Lee, TetrahedronLett. 1997, 38, p. 8207, last line, to p. 8208, 2nd paragraph). Inaddition, B. P. Mundy et al. describe in the above publication that thereaction of methyl vinyl ketone with acrolein methylated in position 2(methacrolein) does not lead to the required hetero-Diels-Alder product,whereas methyl vinyl ketone and acrolein can be converted into therequired hetero-Diels-Alder product. Reaction of 1-methylacrolein with2-methyl-allyl alcohol leads via the hetero-Diels-Alder product to thebicyclic natural substance frontalin (B. P. Mundy, K. B. Lipkowitz, G.W. Dirks, Heterocycles 1977, 6, p. 64, equation 11). Gore et al. wereable to show that 2-methyl-1-penten-3-one and methyl crotonate cannot bereacted to give the required regioisomeric hetero-Diels-Alder product,whereas reaction of 2-methyl-1-penten-3-one with methyl methacrylateleads to the required regioisomeric hetero-Diels-Alder product (W. E.Gore, G. T. Pearce, R. M. Silverstein, J. Org. Chem 1976, 41, pp.603-604). In addition, Smith et al. describe further hetero-Diels-Alderreactions of alkylated acroleins with alkyl-substituted alkyl vinylethers and acrylates (U.S. Pat. No. 2,514,168; C. W. Smith, D. G.Norton, S. A. Ballard, J. Am. Chem. Soc. 1951, pp. 5267-5272).

It is known that introduction of radicals with electron donor propertiesin position 2 of 1-methylacrolein greatly reduces the reactivity of1-methylacrolein as diene component in a Diels-Alder reaction (D. L.Boger, S. M. Weinreb, Hetero Diels-Alder--Methodology in OrganicSynthesis, Academic Press, Inc, 1987, pp. 185 f.). Thus, only oneexample, the Diels-Alder dimerization of3-trimethylsilyloxy-3-buten-2-one (position 3 of 3-buten-2-onecorresponds to position 2 of 1-methylacrolein), is known in which thedimerization of methylacrolein with a silyloxy radical in position 2succeeded in a Diels-Alder reaction (S. Murai; I. Ryu, Y. Kadono, H.Katayama, K. Kondo, N. Sonoda, Chem. Lett. 1977, 1219 f.). MixedDiels-Alder reactions of acroleins having an electron donor as radicalin position 2 with dienophiles are known in only a few cases (D. L.Boger, S. M. Weinreb, loc. cit.). The acroleins moreover have inposition 2 a phenylthio radical and react exclusively with electron-richene components such as ethyl vinyl ether (K. Takaki, M. Yamada, K.Negoro, J. Org. Chem. 1982, 47, 5246-5250). Funk et al. describe amixed, Yb-catalyzed, hetero-Diels-Alder reaction of an acrolein with aphenylacyloxy radical in position 2 with the electron-rich ene componentethyl vinyl ether (J. Org. Chem. 1996, 61, 2599, Reaction (e)).

The reaction according to the invention of the oxy-functionalized dienecomponent of the formula I with the electron-poor ene component IIaffords the corresponding, previously unknown, 3,4-dihydro-2H-pyrans ofthe general formula III. ##STR10## The reaction can be carried out underthe conditions of the hetero-Diels-Alder reactions known per se (D. L.Boger, S. M. Weinreb, loc. cit.).

The reaction of the two components can take place purely thermally,preferably under autogenous pressure, typically at temperatures from100° C. to 250° C. or with the addition of Lewis acids such as tintetrachloride, boron trifluoride, titanium tetrachloride, alkylaluminumdihalides, dialkylaluminum halides, magnesium halides, and halides andtrifluoromethanesulfonates of the lanthanides. The reaction can becarried out in organic solvents such as aliphatic, aromatic, optionallyhalogenated, hydrocarbons or ethers or else without solvent. Preferredorganic solvents are xylene, toluene, heptane, THF, dioxane, methylenechloride or chloroform.

The reaction typically takes from 6 to 24 h. The resulting3,4-dihydro-2H-pyrans can be isolated in a manner known per se, forexample by thermal separation processes such as distillation, from thereaction solution.

The radicals R¹, R² and X in preferred substituted 3,4-dihydro-2H-pyransof the formula III have the following meanings:

R¹ CH₃ or COCH₃,

R² CH₃, 4,8,12-trimethyltridecyl or4,8,12-trimethyl-3,7,11-tridecatrienyl and

X CN, COOH, COOCH₃, COO--CH₂ --CH₂ --OH, COO--CH₂ --CH₂ --Cl, COO--CH₂--CH₂ --N(CH₃)₂, CHO, CH₂ OH, CH₂ OCH₃ or CH(OCH₃)₂ or one of thefollowing structural elements X₁ -X₇. ##STR11##

Examples of combinations of radicals in preferred 3,4-dihydro-2H-pyransof the formula III are the following:

    __________________________________________________________________________    Compound                                                                            R.sup.1                                                                            R.sup.2                      X                                     __________________________________________________________________________      III.001 CH.sub.3 CH.sub.3 CN                                                   - III.002 COCH.sub.3 CH.sub.3 CN                                              - III.003 CH.sub.3                                                                                                   CN R12##                               - III.004 COCH.sub.3                                                                                                 CN R13##                               - III.005 CH.sub.3                                                                                                   CN R14##                               - III.006 COCH.sub.3                                                                                                 CN R15##                               - III.007 CH.sub.3 CH.sub.3 COOH                                              - III.008 COCH.sub.3 CH.sub.3 COOH                                            - III.009 CH.sub.3                                                                                                   COOH 6##                               -  III.0010 COCH.sub.3                                                                                               COOH 7##                               - III.011 CH.sub.3                                                                                                   COOH 8##                               - III.012 COCH.sub.3                                                                                                 COOH 9##                               - III.013 CH.sub.3 CH.sub.3 COOCH.sub.3                                       - III.014 COCH.sub.3 CH.sub.3 COOCH.sub.3                                     - III.015 CH.sub.3                                                                                                   COOCH.sub.3                            - III.016 COCH.sub.3                                                                                                 COOCH.sub.3                            - III.017 CH.sub.3                                                                                                   COOCH.sub.3                            - III.018 COCH.sub.3                                                                                                 COOCH.sub.3                            - III.019 CH.sub.3 CH.sub.3 COO--CH.sub.2 --CH.sub.2 --OH                     - III.020 COCH.sub.3 CH.sub.3 COO--CH.sub.2 --CH.sub.2 --OH                   - III.021 CH.sub.3                                                                                                   COO--CH.sub.2 --CH.sub.2 --OH                                                 - III.022 COCH.sub.3                                                          COO--CH.sub.2 --CH.sub.2 --OH                                                 - III.023 CH.sub.3                                                            COO--CH.sub.2 --CH.sub.2 --OH                                                 - III.024 COCH.sub.3                                                          COO--CH.sub.2 --CH.sub.2 --OH                                                 - III.025 CH.sub.3 CH.sub.3                                                 COO--CH.sub.2 --CH.sub.2 --Cl                                                   - III.026 COCH.sub.3 CH.sub.3                                               COO--CH.sub.2 --CH.sub.2 --Cl                                                   - III.027 CH.sub.3                                                            COO--CH.sub.2 --CH.sub.2 --Cl                                                 - III.028 COCH.sub.3                                                          COO--CH.sub.2 --CH.sub.2 --Cl                                                 - III.029 CH.sub.3                                                            COO--CH.sub.2 --CH.sub.2 --Cl                                                 - III.030 COCH.sub.3                                                          COO--CH.sub.2 --CH.sub.2 --Cl                                                 - III.031 CH.sub.3 CH.sub.3                                                 COO--CH.sub.2 --CH.sub.2 --N(CH.su                                            b.3).sub.2                               - III.032 COCH.sub.3 CH.sub.3 COO--CH.sub.2 --CH.sub.2 --N(CH.sub.3).su                                            b.2                                      - III.033 CH.sub.3                                                                                                   COO--CH.sub.2 --CH.sub.2                                                    --N(CH.sub.3).sub.2                      - III.034 COCH.sub.3                                                                                                 COO--CH.sub.2 --CH.sub.2                                                    --N(CH.sub.3).sub.2                      - III.035 CH.sub.3                                                                                                   COO--CH.sub.2 --CH.sub.2                                                    --N(CH.sub.3).sub.2                      - III.036 COCH.sub.3                                                                                                 COO--CH.sub.2 --CH.sub.2                                                    --N(CH.sub.3).sub.2                      - III.037 CH.sub.3 CH.sub.3 CHO                                               - III.038 COCH.sub.3 CH.sub.3 CHO                                             - III.039 CH.sub.3                                                                                                   CHO 36##                               - III.040 COCH.sub.3                                                                                                 CHO 37##                               - III.041 CH.sub.3                                                                                                   CHO 38##                               - III.042 COCH.sub.3                                                                                                 CHO 39##                               - III.043 CH.sub.3 CH.sub.3 CH.sub.2 OH                                       - III.044 COCH.sub.3 CH.sub.3 CH.sub.2 OH                                     - III.045 CH.sub.3                                                                                                   CH.sub.2 OH                            - III.046 COCH.sub.3                                                                                                 CH.sub.2 OH                            - III.047 CH.sub.3                                                                                                   CH.sub.2 OH                            - III.048 COCH.sub.3                                                                                                 CH.sub.2 OH                            - III.049 CH.sub.3 CH.sub.3 CH.sub.2 OCH.sub.3                                - III.050 COCH.sub.3 CH.sub.3 CH.sub.2 OCH.sub.3                              - III.051 CH.sub.3                                                                                                   CH.sub.2 OCH.sub.3                     - III.052 COCH.sub.3                                                                                                 CH.sub.2 OCH.sub.3                     - III.053 CH.sub.3                                                                                                   CH.sub.2 OCH.sub.3                     - III.054 COCH.sub.3                                                                                                 CH.sub.2 OCH.sub.3                     - III.055 CH.sub.3 CH.sub.3 CH(OCH.sub.3).sub.2                               - III.056 COCH.sub.3 CH.sub.3 CH(OCH.sub.3).sub.2                             - III.057 CH.sub.3                                                                                                   CH(OCH.sub.3).sub.2                    - III.058 COCH.sub.3                                                                                                 CH(OCH.sub.3).sub.2                    - III.059 CH.sub.3                                                                                                   CH(OCH.sub.3).sub.2                    - III.060 COCH.sub.3                                                                                                 CH(OCH.sub.3).sub.2                    - III.061 CH.sub.3 CH.sub.3 X.sub.1                                           - III.062 COCH.sub.3 CH.sub.3 X.sub.1                                         - III.063 CH.sub.3                                                                                                   X.sub.1                                - III.064 COCH.sub.3                                                                                                 X.sub.1                                - III.065 CH.sub.3                                                                                                   X.sub.1                                - III.066 COCH.sub.3                                                                                                 X.sub.1                                - III.067 CH.sub.3 CH.sub.3 X.sub.2                                           - III.068 COCH.sub.3 CH.sub.3 X.sub.2                                         - III.069 CH.sub.3                                                                                                   X.sub.2                                - III.070 COCH.sub.3                                                                                                 X.sub.2                                - III.071 CH.sub.3                                                                                                   X.sub.2                                - III.072 COCH.sub.3                                                                                                 X.sub.2                                - III.073 CH.sub.3 CH.sub.3 X.sub.3                                           - III.074 COCH.sub.3 CH.sub.3 X.sub.3                                         - III.075 CH.sub.3                                                                                                   X.sub.3                                - III.076 COCH.sub.3                                                                                                 X.sub.3                                - III.077 CH.sub.3                                                                                                   X.sub.3                                - III.078 COCH.sub.3                                                                                                 X.sub.3                                - III.079 CH.sub.3 CH.sub.3 X.sub.4                                           - III.080 COCH.sub.3 CH.sub.3 X.sub.4                                         - III.081 CH.sub.3                                                                                                   X.sub.4                                - III.082 COCH.sub.3                                                                                                 X.sub.4                                - III.083 CH.sub.3                                                                                                   X.sub.4                                - III.084 COCH.sub.3                                                                                                 X.sub.4                                - III.085 CH.sub.3 CH.sub.3 X.sub.5                                           - III.086 COCH.sub.3 CH.sub.3 X.sub.5                                         - III.087 CH.sub.3                                                                                                   X.sub.5                                - III.088 COCH.sub.3                                                                                                 X.sub.5                                - III.089 CH.sub.3                                                                                                   X.sub.5                                - III.090 COCH.sub.3                                                                                                 X.sub.5                                - III.091 CH.sub.3 CH.sub.3 X.sub.6                                           - III.092 COCH.sub.3 CH.sub.3 X.sub.6                                         - III.093 CH.sub.3                                                                                                   X.sub.6                                - III.094 COCH.sub.3 C                                                                                               X.sub.6                                - III.095 CH.sub.3                                                                                                   X.sub.6                                - III.096 COCH.sub.3                                                                                                 X.sub.6                                - III.097 CH.sub.3 CH.sub.3 X.sub.7                                           - III.098 COCH.sub.3 CH.sub.3 X.sub.7                                         - III.099 CH.sub.3                                                                                                   X.sub.7                                - III.100 COCH.sub.3                                                                                                 X.sub.7                                - III.101 CH.sub.3                                                                                                   X.sub.7                                - III.102 COCH.sub.3 C                                                                                               X.sub.7#                            __________________________________________________________________________

In the next step of the overall process according to the invention, the3,4-dihydro-2H-pyrans of the general formula III are reacted with anacid. In this way there is acid-catalyzed elimination of the radical R¹and liberation of the enol, which in turn tautomerizes to the5-oxotetrahydropyran of the general formula IV ##STR80##

The substituted 3,4-dihydro-2H-pyrans of the general formula III arereacted with an acid in a manner known per se (J. March, AdvancedOrganic Chemistry, 4^(th) edition, 1992, J. Wiley & sons, pp. 373 f.).Acids mean according to the invention Bronsted acids and their aqueoussolutions. Examples which may be mentioned are mineral acids such asHCl,H₂ SO₄, HClO₄ and optionally halogenated, i.e. Cl-, Br-, I,F-substituted carboxylic acids such as formic acid, acetic acid,propionic acid, chloroacetic acid, trifluoroacetic acid.

Aqueous acid solutions with a low acid concentration, such as 0.01-12 M,are typically sufficient for converting enol ethers into enols. Anexample which may be mentioned is a 2M HCl solution.

The reaction is carried out in an organic solvent as mentioned above,preferably in methylene chloride. The duration and temperature of thereaction depend on the radical R¹. The reaction is typically carried outat room temperature for 2 to 12 h.

In preferred substituted 5-oxotetrahydropyrans of the general formulaIV, the radicals R² and X have the following meanings:

R² CH₃, 4,8,12-trimethyltridecyl or4,8,12-trimethyl-3,7,11-tridecatrienyl and

X CN, COOH, COOCH₃, COO--CH₂ --CH₂ --OH, COO--CH₂ --CH₂ --Cl, COO--CH₂--CH₂ --N(CH₃)₂, CHO, CH₂ OH, CH₂ OCH₃ or CH(OCH₃)₂ or one of thestructural elements X₁ -X₇ as mentioned above for the substituted3,4-dihydro-2H-pyrans of the formula III.

Examples of radical combinations in preferred substituted5-oxotetrahydropyrans of the general formula IV are the following:

    __________________________________________________________________________    Compound                                                                            R.sup.2                      X                                          __________________________________________________________________________      IV.001 CH.sub.3 CN                                                             - IV.002                                                                                                        CN R81##                                    - IV.003                                                                                                        CN R82##                                    - IV.004 CH.sub.3 COOH                                                        - IV.005                                                                                                        COOH 3##                                    - IV.006                                                                                                        COOH 4##                                    - IV.007 CH.sub.3 COOCH.sub.3                                                 - IV.008                                                                                                        COOCH.sub.3                                 - IV.009                                                                                                        COOCH.sub.3                                 - IV.010 CH.sub.3 COO--CH.sub.2 --CH.sub.2 --OH                               - IV.011                                                                                                        COO--CH.sub.2 --CH.sub.2 --OH                                                 - IV.012                                                                      COO--CH.sub.2 --CH.sub.2 --OH                                                 - IV.013 CH.sub.3 COO--CH.sub.2                                             --CH.sub.2 --Cl                               - IV.014                                                                                                        COO--CH.sub.2 --CH.sub.2 --Cl                                                 - IV.015                                                                      COO--CH.sub.2 --CH.sub.2 --Cl                                                 - IV.016 CH.sub.3 COO--CH.sub.2                                             --CH.sub.2 --N(CH.sub.3).sub.2                                                  - IV.017                                                                      COO--CH.sub.2 --CH.sub.2 --N(CH.sub.3                                       ).sub.2                                       - IV.018                                                                                                        COO--CH.sub.2 --CH.sub.2 --N(CH.sub.3                                       ).sub.2                                       - IV.019 CH.sub.3 CHO                                                         - IV.020                                                                                                        CHO 93##                                    - IV.021                                                                                                        CHO 94##                                    - IV.022 CH.sub.3 CH.sub.2 OH                                                 - IV.023                                                                                                        CH.sub.2 OH                                 - IV.024                                                                                                        CH.sub.2 OH                                 - IV.025 CH.sub.3 CH.sub.2 OCH.sub.3                                          - IV.026                                                                                                        CH.sub.2 OCH.sub.3                          - IV.027                                                                                                        CH.sub.2 OCH.sub.3                          - IV.028 CH.sub.3 CH(OCH.sub.3).sub.2                                         - IV.029                                                                                                        CH(OCH.sub.3).sub.2                         - IV.030                                                                                                        CH(OCH.sub.3).sub.2                         - IV.031 CH.sub.3 X.sub.1                                                     - IV.032                                                                                                        X.sub.1 #                                   - IV.033                                                                                                        X.sub.1 #                                   - IV.034 CH.sub.3 X.sub.2                                                     - IV.035                                                                                                        X.sub.2 #                                   - IV.036                                                                                                        X.sub.2 #                                   - IV.037 CH.sub.3 X.sub.3                                                     - IV.038                                                                                                        X.sub.3 #                                   - IV.039                                                                                                        X.sub.3 #                                   - IV.040 CH.sub.3 X.sub.4                                                     - IV.041                                                                                                        X.sub.4 #                                   - IV.042                                                                                                        X.sub.4 #                                   - IV.043 CH.sub.3 X.sub.5                                                     - IV.044                                                                                                        X.sub.5 #                                   - IV.045                                                                                                        X.sub.5 #                                   - IV.046 CH.sub.3 X.sub.6                                                     - IV.047                                                                                                        X.sub.6 #                                   - IV.048                                                                                                        X.sub.6 #                                   - IV.049 CH.sub.3 X.sub.7                                                     - IV.050                                                                                                        X.sub.7 #                                   - IV.051                                                                                                        X.sub.7##                                __________________________________________________________________________

In the next step of the overall process according to the invention, the5-oxotetrahydropyrans of the general formula IV are reacted withsubstituted vinyl ketones of the general formula V in a Robinsonannulation (J. March, Advanced Organic Chemistry, 4^(th) edition, 1992,J. Wiley & sons, pp. 943-944) ##STR115##

The radicals R⁴, R⁵ and R⁶ are, independently of one another, hydrogenor a C₁ -C₄ -alkyl radical as described above for R¹, in particularmethyl. Preferred substituted vinyl ketones of the general formula V are

4-methyl-4-hexen-3-one (R⁴ =R⁵ =R⁶ =methyl),

4-hexen-3-one (R⁴ =hydrogen; R⁵ =R⁶ =methyl),

3-methyl-3-penten-2-one (R⁴ =R⁵ =methyl, R⁶ =hydrogen) and

3-penten-2-one (R⁴ =R⁶ =hydrogen, R⁵ =methyl).

The Robinson annulation can be carried out in a manner known per se (M.E. Jung, Tetrahedron 1976, 32, 3-31; T. Sato et al. Tetrahedron Letters1990, 31, 1581-1584 and publications cited therein, and F. Eicher, K.Wanner, Arch. der Pharmazie 1984, 317, 958-962).

In a preferred embodiment, the reaction is carried out by the enaminemethod known per se (G. Storck et al., J. Am. Chem. Soc. 1963, 85, 207).This entails firstly reacting the substituted 5-oxotetrahydropyrans ofthe general formula IV with secondary amines of the formula VIII

    HN(R.sup.9).sub.2                                          VIII

to give the corresponding enamines of the formula IX ##STR116##

The two R⁹ radicals are identical or different C₁ -C₄ -alkyl radicals asmentioned above for R¹, preferably methyl or ethyl, or a phenyl radicalor the two R⁹ radicals represent a C₂ -C₆ -alkylene radical, such asethylene, propylene, butylene, pentylene, neopentylene or hexylene, or aC₂ -C₆ -alkylene radical where one or two methylene groups are replacedby oxygen, such as --CH₂ --O--CH₂ -- or --CH₂ --CH₂ --O--CH₂ --CH₂ --bridge, to form a cyclic amine.

Preferred secondary amines of the formula VIII are accordingly aminessuch as dimethylamine, diethylamine, pyrrolidine or morpholine, withpyrrolidine or morpholine being particularly preferred.

This entails reacting the substituted 5-oxotetrahydropyrans of thegeneral formula IV in an organic solvent as mentioned above in the caseof the reaction to give the compound of the formula III, firstly withthe secondary amine of the formula VIII and a water-binding desiccantsuch as MgSO₄, Na₂ SO₄ or TiCl₄ to give the enamine of the formula IX.In another embodiment, the water which is formed can be removed byazeotropic distillation with the addition of entrainers such as benzene,toluene, pentane or CH₂ Cl₂. The temperature of the reaction is notcritical and is typically room temperature on use of desiccants. Thereaction typically takes 12 to 24 h.

The enamines of the formula IX formed from IV are then reacted in aMichael addition with the substituted vinyl ketones of the formula V##STR117## to give the corresponding keto enamines of the formula X##STR118## in a manner known per se (Nelson et al., J. Org. Chem. 1969,34, 1225).

The keto enamines of the formula X are then converted into thecorresponding diketone compounds of the formula XI ##STR119## byaddition of acids, for example mineral acids such as hydrochloric acidor sulfuric acid, or aqueous solutions thereof, and the diketones of theformula XI formed as intermediates are converted into the substitutedchromen-6-one derivatives of the general formula VI by addition of abase such as diisopropylethylamine, lithium diethylamide or sodium C₁-C₄ -alcoholates such as sodium methoxide or sodium ethoxide in a mannerknown per se (M. E. Jung, Tetrahedron 1976, 32, 3; R. E. Ganley,Synthesis 1976, 777).

The radicals R², R⁴, R⁵, R⁶ and X in preferred substituted chromen-6-onederivatives of the general formula VI have the following meanings:

R² CH₃, 4,8,12-trimethyltridecyl or4,8,12-trimethyl-3,7,11-tridecatrienyl,

R⁴, R⁵ and R⁶ independently of one another hydrogen or CH₃ and

X CN, COOH, COOCH₃, COO--CH₂ --CH₂ --OH, COO--CH₂ --CH₂ --Cl, COO--CH₂--CH₂ --N(CH₃)₂, CHO, CH₂ OH, CH₂ OCH₃ or CH (OCH₃)₂ or one of thestructural elements X₁ -X₇, as mentioned above for the substituted3,4-dihydro-2H-pyrans of the formula III.

Examples of radical combinations in preferred chromen-6-one derivativesof the formula VI are the following:

    __________________________________________________________________________    Compound                                                                            R.sup.2                      R.sup.4                                                                          R.sup.5                                                                          R.sup.6                                                                          X                                 __________________________________________________________________________    VI.001                                                                              CH.sub.3                     CH.sub.3                                                                         CH.sub.3                                                                         CH.sub.3                                                                         CN                                  VI.002 CH.sub.3 H CH.sub.3 CH.sub.3 CN                                        VI.003 CH.sub.3 CH.sub.3 CH.sub.3 H CN                                        VI.004 CH.sub.3 H CH.sub.3 H CN                                                - VI.005                                                                                                                 CH.sub.3 CH.sub.3 CH.sub.3                                                  CN                                   - VI.006                                                                                                                 H CH.sub.3 CH.sub.3 CN                                                        - VI.007                                                                      CH.sub.3 CH.sub.3 H CN                                                        - VI.008                                                                      H CH.sub.3 H CN                    - VI.009                                                                                                                 CH.sub.3 CH.sub.3 CH.sub.3                                                  CN                                   - VI.010                                                                                                                 H CH.sub.3 CH.sub.3 CN                                                        - VI.011                                                                      CH.sub.3 CH.sub.3 H CN                                                        - VI.012                                                                      H CH.sub.3 H CN                    - VI.013 CH.sub.3 CH.sub.3 CH.sub.3 CH.sub.3 COOH                            VI.014 CH.sub.3 H CH.sub.3 CH.sub.3 COOH                                      VI.015 CH.sub.3 CH.sub.3 CH.sub.3 H COOH                                      VI.016 CH.sub.3 H CH.sub.3 H COOH                                              - VI.017                                                                                                                 CH.sub.3 CH.sub.3 CH.sub.3                                                  COOH                                 - VI.018                                                                                                                 H CH.sub.3 CH.sub.3 COOH                                                      - VI.019                                                                      CH.sub.3 CH.sub.3 H COOH                                                      - VI.020                                                                      H CH.sub.3 H COOH                  - VI.021                                                                                                                 CH.sub.3 CH.sub.3 CH.sub.3                                                  COOH                                 - VI.022                                                                                                                 H CH.sub.3 CH.sub.3 COOH                                                      - VI.023                                                                      CH.sub.3 CH.sub.3 H COOH                                                      - VI.024                                                                      H CH.sub.3 H COOH                  - VI.025 CH.sub.3 CH.sub.3 CH.sub.3 CH.sub.3 COOCH.sub.3                     VI.026 CH.sub.3 H CH.sub.3 CH.sub.3 COOCH.sub.3                               VI.027 CH.sub.3 CH.sub.3 CH.sub.3 H COOCH.sub.3                               VI.028 CH.sub.3 H CH.sub.3 H COOCH.sub.3                                       - VI.029                                                                                                                 CH.sub.3 CH.sub.3 CH.sub.3                                                  COOCH.sub.3                          - VI.030                                                                                                                 H CH.sub.3 CH.sub.3                                                         COOCH.sub.3                          - VI.031                                                                                                                 CH.sub.3 CH.sub.3 H                                                         COOCH.sub.3                          - VI.032                                                                                                                 H CH.sub.3 H COOCH.sub.3                                                      - VI.033                                                                      CH.sub.3 CH.sub.3 CH.sub.3                                                  COOCH.sub.3                          - VI.034                                                                                                                 H CH.sub.3 CH.sub.3                                                         COOCH.sub.3                          - VI.035                                                                                                                 CH.sub.3 CH.sub.3 H                                                         COOCH.sub.3                          - VI.036                                                                                                                 H CH.sub.3 H COOCH.sub.3                                                      - VI.037 CH.sub.3 CH.sub.3                                                  CH.sub.3 CH.sub.3 COO--CH.sub.                                                2 --CH.sub.2 --OH                   VI.038 CH.sub.3 H CH.sub.3 CH.sub.3 COO--CH.sub.2 --CH.sub.2 --OH                                                        VI.039 CH.sub.3 CH.sub.3                                                     CH.sub.3 H COO--CH.sub.2                                                      --CH.sub.2 --OH                     VI.040 CH.sub.3 H CH.sub.3 H COO--CH.sub.2 --CH.sub.2 --OH                     - VI.041                                                                                                                 CH.sub.3 CH.sub.3 CH.sub.3                                                  COO--CH.sub.2 --CH.sub.2 --OH        - VI.042                                                                                                                 H CH.sub.3 CH.sub.3                                                         COO--CH.sub.2 --CH.sub.2 --OH        - VI.043                                                                                                                 CH.sub.3 CH.sub.3 H                                                         COO--H.sub.2 --CH.sub.2 --OH                                                    - VI.044                                                                      H CH.sub.3 H COO--CH.sub.2                                                  --CH.sub.2 --OH                      - VI.045                                                                                                                 CH.sub.3 CH.sub.3 CH.sub.3                                                  COO--CH.sub.2 --CH.sub.2 --OH        - VI.046                                                                                                                 H CH.sub.3 CH.sub.3                                                         COO--CH.sub.2 --CH.sub.2 --OH        - VI.047                                                                                                                 CH.sub.3 CH.sub.3 H                                                         COO--CH.sub.2 --CH.sub.2 --OH        - VI.048                                                                                                                 H CH.sub.3 H COO--CH.sub.2                                                  --CH.sub.2 --OH                      - VI.049 CH.sub.3 CH.sub.3 CH.sub.3 CH.sub.3 COO--CH.sub.2 --CH.sub.2                                                  --Cl                                VI.050 CH.sub.3 H CH.sub.3 CH.sub.3 COO--CH.sub.2 --CH.sub.2 --Cl                                                        VI.051 CH.sub.3 CH.sub.3                                                     CH.sub.3 H COO--CH.sub.2                                                      --CH.sub.2 --Cl                     VI.052 CH.sub.3 H CH.sub.3 H COO--CH.sub.2 --CH.sub.2 --Cl                     - VI.053                                                                                                                 CH.sub.3 CH.sub.3 CH.sub.3                                                  COO--CH.sub.2 --CH.sub.2 --Cl        - VI.054                                                                                                                 H CH.sub.3 CH.sub.3                                                         COO--CH.sub.2 --CH.sub.2 --Cl        - VI.055                                                                                                                 CH.sub.3 CH.sub.3 H                                                         COO--CH.sub.2 --CH.sub.2 --Cl        - VI.056                                                                                                                 H CH.sub.3 H COO--CH.sub.2                                                  --CH.sub.2 --Cl                      - VI.057                                                                                                                 CH.sub.3 CH.sub.3 CH.sub.3                                                  COO--CH.sub.2 --CH.sub.2 --Cl        - VI.058                                                                                                                 H CH.sub.3 CH.sub.3                                                         COO--CH.sub.2 --CH.sub.2 --Cl        - VI.059                                                                                                                 CH.sub.3 CH.sub.3 H                                                         COO--CH.sub.2 --CH.sub.2 --Cl        - VI.060                                                                                                                 H CH.sub.3 H COO--CH.sub.2                                                  --CH.sub.2 --Cl                      - VI.061 CH.sub.3 CH.sub.3 CH.sub.3 CH.sub.3 COO--CH.sub.2 --CH.sub.2                                                  --N(CH.sub.3).sub.2                 VI.062 CH.sub.3 H CH.sub.3 CH.sub.3 COO--CH.sub.2 --CH.sub.2 --N(CH.sub.                                                3).sub.2                            VI.063 CH.sub.3 CH.sub.3 CH.sub.3 H COO--CH.sub.2 --CH.sub.2 --N(CH.sub.                                                3).sub.2                            VI.064 CH.sub.3 H CH.sub.3 H COO--CH.sub.2 --CH.sub.2 --N(CH.sub.3).sub.                                                2                                    - VI.065                                                                                                                 CH.sub.3 CH.sub.3 CH.sub.3                                                  COO--CH.sub.2 --CH.sub.2                                                      --N(CH.sub.3).sub.2                  - VI.066                                                                                                                 H CH.sub.3 CH.sub.3                                                         COO--CH.sub.2 --CH.sub.2                                                      --N(CH.sub.3).sub.2                  - VI.067                                                                                                                 CH.sub.3 CH.sub.3 H                                                         COO--CH.sub.2 --CH.sub.2                                                      --N(CH.sub.3).sub.2                  - VI.068                                                                                                                 H CH.sub.3 H COO--CH.sub.2                                                  --CH.sub.2 --N(CH.sub.3).sub.2       - VI.069                                                                                                                 CH.sub.3 CH.sub.3 CH.sub.3                                                  COO--CH.sub.2 --CH.sub.2                                                      --N(CH.sub.3).sub.2                  - VI.070                                                                                                                 H CH.sub.3 CH.sub.3                                                         COO--CH.sub.2 --CH.sub.2                                                      --N(CH.sub.3).sub.2                  - VI.071                                                                                                                 CH.sub.3 CH.sub.3 H                                                         COO--CH.sub.2 --CH.sub.2                                                      --N(CH.sub.3).sub.2                  - VI.072                                                                                                                 H CH.sub.3 H COO--CH.sub.2                                                  --CH.sub.2 --N(CH.sub.3                                                         - VI.073 CH.sub.3 CH.sub.3                                                  CH.sub.3 CH.sub.3 CHO                                                          VI.074 CH.sub.3 H CH.sub.3                                                   CH.sub.3 CHO                        VI.075 CH.sub.3 CH.sub.3 CH.sub.3 H CHO                                       VI.076 CH.sub.3 H CH.sub.3 H CHO                                               - VI.077                                                                                                                 CH.sub.3 CH.sub.3 CH.sub.3                                                  CHO                                  - VI.078                                                                                                                 H CH.sub.3 CH.sub.3 CHO                                                       - VI.079                                                                      CH.sub.3 CH.sub.3 H CHO                                                       - VI.080                                                                      H CH.sub.3 H CHO                   - VI.081                                                                                                                 CH.sub.3 CH.sub.3 CH.sub.3                                                  CHO                                  - VI.082                                                                                                                 H CH.sub.3 CH.sub.3 CHO                                                       - VI.083                                                                      CH.sub.3 CH.sub.3 H CHO                                                       - VI.084                                                                      H CH.sub.3 H CHO                   - VI.085 CH.sub.3 CH.sub.3 CH.sub.3 CH.sub.3 CH.sub.2 OH                     VI.086 CH.sub.3 H CH.sub.3 CH.sub.3 CH.sub.2 OH                               VI.087 CH.sub.3 CH.sub.3 CH.sub.3 H CH.sub.2 OH                               VI.088 CH.sub.3 H CH.sub.3 H CH.sub.2 OH                                       - VI.089                                                                                                                 CH.sub.3 CH.sub.3 CH.sub.3                                                  CH.sub.2 OH                          - VI.090                                                                                                                 H CH.sub.3 CH.sub.3                                                         CH.sub.2 OH                          - VI.091                                                                                                                 CH.sub.3 CH.sub.3 H                                                         CH.sub.2 OH                          - VI.092                                                                                                                 H CH.sub.3 H CH.sub.2 OH                                                      - VI.093                                                                      CH.sub.3 CH.sub.3 CH.sub.3                                                  CH.sub.2 OH                          - VI.094                                                                                                                 H CH.sub.3 CH.sub.3                                                         CH.sub.2 OH                          - VI.095                                                                                                                 CH.sub.3 CH.sub.3 H                                                         CH.sub.2 OH                          - VI.096                                                                                                                 H CH.sub.3 H CH.sub.2 OH                                                      - VI.097 CH.sub.3 CH.sub.3                                                  CH.sub.3 CH.sub.3 CH.sub.2                                                    OCH.sub.3                           VI.098 CH.sub.3 H CH.sub.3 CH.sub.3 CH.sub.2 OCH.sub.3                        VI.099 CH.sub.3 CH.sub.3 CH.sub.3 H CH.sub.2 OCH.sub.3                        VI.100 CH.sub.3 H CH.sub.3 H CH.sub.2 OCH.sub.3                                - VI.101                                                                                                                 CH.sub.3 CH.sub.3 CH.sub.3                                                  CH.sub.2 OCH.sub.3                   - VI.102                                                                                                                 H CH.sub.3 CH.sub.3                                                         CH.sub.2 OCH.sub.3                   - VI.103                                                                                                                 CH.sub.3 CH.sub.3 H                                                         CH.sub.2 OCH.sub.3                   - VI.104                                                                                                                 H CH.sub.3 H CH.sub.2                                                       OCH.sub.3                            - VI.105                                                                                                                 CH.sub.3 CH.sub.3 CH.sub.3                                                  CH.sub.2 OCH.sub.3                   - VI.106                                                                                                                 H CH.sub.3 CH.sub.3                                                         CH.sub.2 OCH.sub.3                   - VI.107                                                                                                                 CH.sub.3 CH.sub.3 H                                                         CH.sub.2 OCH.sub.3                   - VI.108                                                                                                                 H CH.sub.3 H CH.sub.2                                                       OCH.sub.3                            - VI.109 CH.sub.3 CH.sub.3 CH.sub.3 CH.sub.3 CH(OCH.sub.3).sub.2                                                        VI.110 CH.sub.3 H CH.sub.3                                                   CH.sub.3 CH(OCH.sub.3).sub.2                                                   VI.111 CH.sub.3 CH.sub.3                                                     CH.sub.3 H CH(OCH.sub.3).sub.2      VI.112 CH.sub.3 H CH.sub.3 H CH(OCH.sub.3).sub.2                               - VI.113                                                                                                                 CH.sub.3 CH.sub.3 CH.sub.3                                                  CH(OCH.sub.3).sub.2                  - VI.114                                                                                                                 H CH.sub.3 CH.sub.3                                                         CH(OCH.sub.3).sub.2                  - VI.115                                                                                                                 CH.sub.3 CH.sub.3 H                                                         CH(OCH.sub.3).sub.2                  - VI.116                                                                                                                 H CH.sub.3 H CH(OCH.sub.3).s                                                ub.2                                 - VI.117                                                                                                                 CH.sub.3 CH.sub.3 CH.sub.3                                                  CH(OCH.sub.3).sub.2                  - VI.118                                                                                                                 H CH.sub.3 CH.sub.3                                                         CH(OCH.sub.3).sub.2                  - VI.119                                                                                                                 CH.sub.3 CH.sub.3 H                                                         CH(OCH.sub.3).sub.2                  - VI.120                                                                                                                 H CH.sub.3 H CH(OCH.sub.3).s                                                ub.2                                 - VI.121 CH.sub.3 CH.sub.3 CH.sub.3 CH.sub.3 X.sub.1                         VI.122 CH.sub.3 H CH.sub.3 CH.sub.3 x1                                        VI.123 CH.sub.3 CH.sub.3 CH.sub.3 H X.sub.1                                   VI.124 CH.sub.3 H CH.sub.3 H X.sub.1                                           - VI.125                                                                                                                 CH.sub.3 CH.sub.3 CH.sub.3                                                  x1                                   - VI.126                                                                                                                 H CH.sub.3 CH.sub.3 x1                                                        - VI.127                                                                      CH.sub.3 CH.sub.3 H X.sub.1        - VI.128                                                                                                                 H CH.sub.3 H X.sub.1                                                          - VI.129                                                                      CH.sub.3 CH.sub.3 CH.sub.3                                                  X.sub.1                              - VI.130                                                                                                                 H CH.sub.3 CH.sub.3 X.sub.1        - VI.131                                                                                                                 CH.sub.3 CH.sub.3 H X.sub.1        - VI.132                                                                                                                 H CH.sub.3 H X.sub.1                                                          - VI.133 CH.sub.3 CH.sub.3                                                  CH.sub.3 CH.sub.3 X.sub.2                                                      VI.134 CH.sub.3 H CH.sub.3                                                   CH.sub.3 X.sub.2                    VI.135 CH.sub.3 CH.sub.3 CH.sub.3 H X.sub.2                                   VI.136 CH.sub.3 H CH.sub.3 H X.sub.2                                           - VI.137                                                                                                                 CH.sub.3 CH.sub.3 CH.sub.3                                                  X.sub.2                              - VI.138                                                                                                                 H CH.sub.3 CH.sub.3 x2                                                        - VI.139                                                                      CH.sub.3 CH.sub.3 H X.sub.2        - VI.140                                                                                                                 H CH.sub.3 H X.sub.2                                                          - VI.141                                                                      CH.sub.3 CH.sub.3 CH.sub.3                                                  X.sub.2                              - VI.142                                                                                                                 H CH.sub.3 CH.sub.3 X.sub.2        - VI.143                                                                                                                 CH.sub.3 CH.sub.3 H X.sub.2        - VI.144                                                                                                                 H CH.sub.3 H X.sub.2                                                          - VI.145 CH.sub.3 CH.sub.3                                                  CH.sub.3 CH.sub.3 X.sub.3                                                      VI.146 CH.sub.3 H CH.sub.3                                                   CH.sub.3 X.sub.3                    VI.147 CH.sub.3 CH.sub.3 CH.sub.3 H X.sub.3                                   VI.148 CH.sub.3 H CH.sub.3 H X.sub.3                                           - VI.149                                                                                                                 CH.sub.3 CH.sub.3 CH.sub.3                                                  X.sub.3                              - VI.150                                                                                                                 H CH.sub.3 CH.sub.3 X.sub.3        - VI.151                                                                                                                 CH.sub.3 CH.sub.3 H X.sub.3        - VI.152                                                                                                                 H CH.sub.3 H X.sub.3                                                          - VI.153                                                                      CH.sub.3 CH.sub.3 CH.sub.3                                                  X.sub.3                              - VI.154                                                                                                                 H CH.sub.3 CH.sub.3 X.sub.3        - VI.155                                                                                                                 CH.sub.3 CH.sub.3 H X.sub.3        - VI.156                                                                                                                 H CH.sub.3 H X.sub.3                                                          - VI.157 CH.sub.3 CH.sub.3                                                  CH.sub.3 CH.sub.3 X.sub.4                                                      VI.158 CH.sub.3 H CH.sub.3                                                   CH.sub.3 X.sub.4                    VI.159 CH.sub.3 CH.sub.3 CH.sub.3 H X.sub.4                                   VI.160 CH.sub.3 H CH.sub.3 H X.sub.4                                           - VI.161                                                                                                                 CH.sub.3 CH.sub.3 CH.sub.3                                                  x4                                   - VI.162                                                                                                                 H CH.sub.3 CH.sub.3 x4                                                        - VI.163                                                                      CH.sub.3 CH.sub.3 H X.sub.4        - VI.164                                                                                                                 H CH.sub.3 H X.sub.4                                                          - VI.165                                                                      CH.sub.3 CH.sub.3 CH.sub.3                                                  X.sub.4                              - VI.166                                                                                                                 H CH.sub.3 CH.sub.3 X.sub.4        - VI.167                                                                                                                 CH.sub.3 CH.sub.3 H X.sub.4        - VI.168                                                                                                                 H CH.sub.3 H x4                    - VI.169 CH.sub.3 CH.sub.3 CH.sub.3 CH.sub.3 X.sub.5                         VI.170 CH.sub.3 H CH.sub.3 CH.sub.3 X.sub.5                                   VI.171 CH.sub.3 CH.sub.3 CH.sub.3 H X.sub.5                                   VI.172 CH.sub.3 H CH.sub.3 H X.sub.5                                           - VI.173                                                                                                                 CH.sub.3 CH.sub.3 CH.sub.3                                                  X.sub.5                              - VI.174                                                                                                                 H CH.sub.3 CH.sub.3 X.sub.5        - VI.175                                                                                                                 CH.sub.3 CH.sub.3 H X.sub.5        - VI.176                                                                                                                 H CH.sub.3 H X.sub.5                                                          - VI.177                                                                      CH.sub.3 CH.sub.3 CH.sub.3                                                  X.sub.5                              - VI.178                                                                                                                 H CH.sub.3 CH.sub.3 X.sub.5        - VI.179                                                                                                                 CH.sub.3 CH.sub.3 H X.sub.5        - VI.180                                                                                                                 H CH.sub.3 H X.sub.5                                                          - VI.181 CH.sub.3 CH.sub.3                                                  CH.sub.3 CH.sub.3 X.sub.6                                                      VI.182 CH.sub.3 H CH.sub.3                                                   CH.sub.3 X.sub.6                    VI.183 CH.sub.3 CH.sub.3 CH.sub.3 H X.sub.6                                   VI.184 CH.sub.3 H CH.sub.3 H X.sub.6                                           - VI.185                                                                                                                 CH.sub.3 CH.sub.3 CH.sub.3                                                  X.sub.6                              - VI.186                                                                                                                 H CH.sub.3 CH.sub.3 X.sub.6        - VI.187                                                                                                                 CH.sub.3 CH.sub.3 H X.sub.6        - VI.188                                                                                                                 H CH.sub.3 H X.sub.6                                                          - VI.189                                                                      CH.sub.3 CH.sub.3 CH.sub.3                                                  X.sub.6                              - VI.190                                                                                                                 CH.sub.3 CH.sub.3 X.sub.6                                                     - VI.191                                                                      CH.sub.3 CH.sub.3 H X.sub.6        - VI.192                                                                                                                 H CH.sub.3 H X.sub.6                                                          - VI.193 CH.sub.3 CH.sub.3                                                  CH.sub.3 CH.sub.3 X.sub.7                                                      VI.194 CH.sub.3 H CH.sub.3                                                   CH.sub.3 X.sub.7                    VI.195 CH.sub.3 CH.sub.3 CH.sub.3 H X.sub.7                                   VI.196 CH.sub.3 H CH.sub.3 H X.sub.7                                           - VI.197                                                                                                                 CH.sub.3 CH.sub.3 CH.sub.3                                                  x7                                   - VI.198                                                                                                                 H CH.sub.3 CH.sub.3 X.sub.7        - VI.199                                                                                                                 CH.sub.3 CH.sub.3 H X.sub.7        - VI.200                                                                                                                 H CH.sub.3 H X.sub.7                                                          - VI.201                                                                      CH.sub.3 CH.sub.3 CH.sub.3                                                  X.sub.7                              - VI.202                                                                                                                 H CH.sub.3 CH.sub.3 x7                                                        - VI.203                                                                      CH.sub.3 CH.sub.3 H X.sub.7        - VI.204                                                                                                                 H CH.sub.3 H X.sub.7            __________________________________________________________________________

In the last step of the process according to the invention, thechromen-6-one derivatives of the general formula VI are dehydrogenatedby addition of dehydrogenating agents such as Pd(C), MnO₂, S, Se or DDQ(dichlorodicyanoquinone;4,5-dichloro-3,6-dioxo-1,4-cyclohexadiene-1,2-dicarbonitrile) in amanner known per se to give the substituted chromans of the generalformula VII (R.P. Fu, R. G. Harvey, Chem. Rev. 1978, 78, 317).

The process according to the invention is a novel process for preparingchroman derivatives of the general formula VII. The process moreovermakes use of low-cost starting materials. In addition, the processavoids the well-known problem of regioselectivity in electrophilicsubstitutions on electron-rich aromatic systems in prior art processesand makes it possible to construct a flexible substituent pattern on thearomatic moiety in the chroman structure. Besides this, the processproceeds via novel, easily handled intermediates which in turn arevaluable intermediates for novel pharmaceutical agents, flavorings andfragrances, and vitamins and food additives.

The following examples illustrate the invention.

EXAMPLE 1 Preparation of2-methyl-2-methoxycarbonyl-5-methoxy-3,4-dihydro-2H-pyran (IIIa)##STR256## 1a) Preparation without addition of Lewis acids

0.2 mol of α-methoxyacrolein was dissolved in 100 ml of xylene and then0.2 mol of methyl methacrylate was added. The mixture was stirred at180° C. under autogenous pressure for 12 h. Vacuum distillation of themixture resulted in isolation of 0.08 mol (40% of theory) of the product2-methyl-2-methoxycarbonyl-5-methoxy-3,4-dihydro-2H-pyran as thecolorless oil.

MS(EI): 186 (M+, 48%), 155 (33%), 127 (62%)

¹³ C-NMR: 174.5, 140.5, 122.9, 76.1, 55.0, 52.4, 29.8, 25.1, 19.9

1b) Preparation with addition of Lewis acids

0.2 mol of α-methoxyacrolein was dissolved in 100 ml of xylene. Then,while cooling, 10 mmol of tin tetrachloride and then 0.2 mol of methylmethacrylate were added, and the mixture was stirred at 120° C. underautogenous pressure for 12 h. Vacuum distillation of the mixtureresulted in isolation of 32% of theory of the product of2-methyl-2-methoxycarbonyl-5-methoxy-3,4-dihydro-2H-pyran as a paleyellow oil. See 1a for physical data.

EXAMPLE 2 Preparation of2-methyl-2-formyl-5-methoxy-3,4-dihydro-2H-pyran (IIIb) ##STR257##

0.2 mol of α-methoxyacrolein was dissolved in 100 ml of xylene and then0.2 mol of methacrolein was added. The mixture was stirred at 180° C.under autogenous pressure for 12 h. Vacuum distillation of the mixtureresulted in isolation of 0.11 mol (55% of theory) of the product2-methyl-2-formyl-5-methoxy-3,4-dihydro-2H-pyran as a colorless oil.

MS(CI): 156 (M+, 12%), 141 (14%), 87 (100%)

EXAMPLE 3 Preparation of2-methyl-2-hydroxymethyl-5-methoxy-3,4-dihydro-2H-pyran (IIIc)##STR258##

0.2 mol of α-methoxyacrolein was dissolved in 100 ml of xylene and then0.2 ml of methallyl alcohol was added. The mixture was stirred at 180°C. under autogenous pressure for 12 h. Vacuum distillation of themixture resulted in isolation of 0.15 mol (75% of theory) of the product2-methyl-2-hydroxymethyl-5-methoxy-3,4-dihydro-2H-pyran as a colorlessoil.

MS(CI): 158 (M+, 4%), 141 (9%), 127 (33%), 87 (100%)

EXAMPLE 4 Preparation of 2-hydroxyethyl2-methyl-5-methoxy-3,4-dihydro-2H-pyran-2-carboxylate (IIId) ##STR259##

0.2 mol of α-methoxyacrolein was dissolved in 100 ml of xylene and then0.2 mol of 2-hydroxyethyl methacrylate was added. The mixture wasstirred at 180° C. under autogenous pressure for 12 h. Vacuumdistillation of the mixture resulted in isolation of the product2-hydroxyethyl 2-methyl-5-methoxy-3,4-dihydro-2H-pyran- 2-carboxylate asa colorless oil in a yield of 48%.

MS(EI): 216 (M+, 88%), 127 (100%), 185 (10%), 154 (9%)

EXAMPLE 5 Preparation of 2-chloroethyl2-methyl-5-methoxy-3,4-dihydro-2H-pyran-2-carboxylate (IIIe) ##STR260##

0.2 mol of α-methoxyacrolein was dissolved in 100 ml of xylene and then0.2 mol of 2-chloroethyl methacrylate was added. The mixture was stirredat 180° C. under autogenous pressure for 12 h. Vacuum distillation ofthe mixture resulted in isolation of the product 2-chloroethyl2-methyl-5-methoxy-3,4-dihydro-2H-pyran-2-carboxylate as a colorless oilin a yield of 45%.

MS(EI): 234 (M+, 12%), 199 (27%), 113 (100%)

EXAMPLE 6 Preparation of 2-dimethylaminoethyl2-methyl-5-methoxy-3,4-dihydro-2H-pyran-2-carboxylate (IIIf) ##STR261##

0.2 mol of α-methoxyacrolein was dissolved in 100 ml of xylene and then0.2 mol of 2-dimethylaminoethyl methacrylate was added. The mixture wasstirred at 180° C. under autogenous pressure for 12 h. Columnchromatography of the mixture resulted in isolation of the product2-dimethylaminoethyl2-methyl-5-methoxy-3,4-dihydro-2H-pyran-2-carboxylate in a yield of 52%.

NMR: δ(¹³ C) in [ppm]: 198.1; 173.6; 140.5; 123.1; 62.6; 57.2; 55.1;45.2; 29.8; 24.5; 21.6

EXAMPLE 7 Preparation of 2-chloroethyl2-methyl-5-oxotetrahydropyran-2-carboxylate (IVe) by hydrolyzing2-chloroethyl 2-methyl-5-methoxy-3,4-dihydro-2H-pyran-2-carboxylate(IIIg) ##STR262##

3.72 g (20 mmol) of 2-chloroethyl2-methyl-5-methoxy-3,4-dihydro-2H-pyran-2-carboxylate (IIIe) weredissolved in 20 ml of methylene chloride and, at RT, 20 ml of aqueousHCl solution (2M) were added and the mixture was stirred until precursorwas no longer detectable by a TLC check (4 h). The phases wereseparated. After drying of the organic phase and removal of the solvent,3.20 g (74%) of 2-chloroethyl2-methyl-5-oxo-tetrahydropyran-2-carboxylate (IVe) remain as a yellowoil.

MS(EI): 220 (M+, 10%), 151 (4%), 113 (100%)

We claim:
 1. A process for preparing substituted chroman derivatives of the general formula VII, ##STR263## where X is the group --CN, --COOR³, --CHO, --CH₂ OR⁷ or --CH(OR⁸)₂,R² is a C₁ -C₂₃ -alkyl, C₂ -C₂₃ -alkenyl, C₆ -C₁₈ -aryl or C₇ -C₁₈ -aralkyl radical, R³ is hydrogen, a C₁ -C₄ -alkyl radical, a C₁ -C₄ -haloalkyl radical, a C₁ -C₄ -hydroxyalkyl radical or a C₁ -C₄ -aminoalkyl radical, R⁴, R⁵, R⁶ are, independently of one another, hydrogen or a C₁ -C₄ -alkyl radical, R⁷ is hydrogen or a C₁ -C₄ -alkyl radical, R⁸ is a C₁ -C₄ -alkyl radical, or the two radicals are a C₂ -C₆ -alkylene radical which links the two oxygen atoms to form a cyclic acetal and is optionally branched or may carry one or two carboxyl groups, cyclohexyl or phenyl radicals,which comprises, in a first step, reacting substituted acroleins of the general formula I, ##STR264## where R¹ is a C₁ -C₄ -alkyl, C₆ -C₁₈ -aryl, C₇ -C₁₈ -aralkyl, C₁ -C₄ -acyl, a halogenated C₁ -C₄ -acyl radical or another acid-labile protective group for the hydroxyl group, with acrylonitriles, acrylates, acroleins, acrolein acetals, allyl alcohols or allyl ethers of the general formula II ##STR265## to give the corresponding 3,4-dihydro-2H-pyrans of the general formula III ##STR266## and, in a second step, reacting the latter with an acid to give the corresponding 5-oxotetrahydropyrans of the general formula IV ##STR267## and, in a third step, reacting the latter with substituted vinyl ketones of the general formula V ##STR268## to give the corresponding chromen-6-one derivatives of the general formula VI ##STR269## and, in a 4th step, dehydrogenating the latter to give the substituted chroman derivatives of the general formula VII.
 2. A substituted 3,4-dihydro-2H-pyran of the formula III, ##STR270## where R¹ is a C₁ -C₄ -alkyl, C₆ -C₁₈ -aryl, C₇ -C₁₈ -aralkyl, C₁ -C₄ -acyl, a halogenated C₁ -C₄ -acyl radical or another acid-labile protective group for the hydroxyl group,X is the group --CN, --COOR³, --CHO, --CH₂ OR⁷ or --CH(OR⁸)₂, R² is a C₁ -C₂₃ -alkyl, C₂ -C₂₃ -alkenyl, C₆ -C₁₈ -aryl or C₇ -C₁₈ -aralkyl radical, R³ is hydrogen, a C₁ -C₄ -alkyl radical, a C₁ -C₄ -haloalkyl radical, a C₁ -C₄ -hydroxyalkyl radical or a C₁ -C₄ -aminoalkyl radical, R⁷ is hydrogen or a C₁ -C₄ -alkyl radical, R⁸ is a C₁ -C₄ -alkyl radical, or the two radicals are a C₂ -C₆ -alkylene radical which links the two oxygen atoms to form a cyclic acetal and is optionally branched or may carry one or two carboxyl groups, cyclohexyl or phenyl radicals.
 3. A substituted 3,4-dihydro-2H-pyran of the formula III as claimed in claim 2, where the substituents have the following meanings:R¹ CH₃ or COCH₃, R² CH₃, 4,8,12-trimethyltridecyl or 4,8,12-trimethyl-3,7,11-tridecatrienyl and X CN, COOH, COOCH₃, COO--CH₂ --CH₂ --OH, COO--CH₂ --CH₂ --Cl, COO--CH₂ --CH₂ --N(CH₃)₂, CHO, CH₂ OH, CH₂ OCH₃ or CH(OCH₃)₂ or one of the following structural elements X₁ -X₇. ##STR271##
 4. A process for preparing substituted 3,4-dihydro-2H-pyrans of the general formula III as claimed in claim 2, which comprises reacting substituted acroleins of the general formula I, with acrylonitriles, acrylates, acroleins, acrolein acetals, allyl alcohols or allyl ethers of the general formula II, ##STR272##
 5. A substituted 5-oxotetrahydropyran of the formula IV, whereX is the group --CN, --COOR³, --CHO, --CH₂ OR⁷ or --CH(OR⁸)₂, R² is a C₁ -C₂₃ -alkyl, C₂ -C₂₃ -alkenyl, C₆ -C₁₈ -aryl or C₇ -C₁₈ -aralkyl radical, R³ is hydrogen, a C₁ -C₄ -alkyl radical, a C₁ -C₄ -haloalkyl radical, a C₁ -C₄ -hydroxyalkyl radical or a C1-C4-aminoalkyl radical, R⁷ is hydrogen or a C₁ -C₄ -alkyl radical, R⁸ is a C₁ -C₄ -alkyl radical, or the two radicals are a C₂ -C₆ -alkylene radical which links the two oxygen atoms to form a cyclic acetal and is optionally branched or may carry one or two carboxyl groups, cyclohexyl or phenyl radicals.
 6. A substituted 5-oxotetrahydropyran of the formula IV as claimed in claim 5, where the substituents have the following meanings:R² CH₃, 4,8,12-trimethyltridecyl or 4,8,12-trimethyl-3,7,11-tridecatrienyl and X CN, COOH, COOCH₃, COO--CH₂ --CH₂ --OH, COO--CH₂ --CH₂ --Cl, COO--CH₂ --CH₂ --N(CH₃)₂, CHO, CH₂ OH, CH₂ OCH₃ or CH(OCH₃)₂ or one of the following structural elements X₁ -X₇. ##STR273##
 7. A process for preparing substituted 5-oxotetrahydropyrans of the formula IV as claimed in claim 6, which comprises reacting substituted acroleins of the general formula I, whereR¹ is a C₁ -C₄ -alkyl, C₆ -C₁₈ -aryl, C₇ -C₁₈ -aralkyl, C₁ -C₄ -acyl, a halogenated C₁ -C₄ -acyl radical or another acid-labile protective group for the hydroxyl group,with acrylonitriles, acrylates, acroleins, acrolein acetals, allyl alcohols or allyl ethers of the general formula II ##STR274## to give the corresponding 3,4-dihydro-2H-pyrans of the general formula III ##STR275## and, in a second step, converting the latter with an acid into the 5-oxotetrahydropyrans of the formula IV.
 8. A substituted chromen-6-one derivative of the formula VI, ##STR276## where X is the group --CN, --COOR³, --CHO, --CH₂ OR⁷ or --CH(OR⁸)₂,R² is a C₁ -C₂₃ -alkyl, C₂ -C₂₃ -alkenyl, C₆ -C₁₈ -aryl or C₇ -C₁₈ -aralkyl radical, R³ is hydrogen, a C₁ -C₄ -alkyl radical, a C₁ -C₄ -haloalkyl radical, a C₁ -C₄ -hydroxyalkyl radical or a C₁ -C₄ -aminoalkyl radical, R⁴, R⁵, R⁶, independently of one another, are hydrogen or a C₁ -C₄ -alkyl radical, R⁷ is hydrogen or a C₁ -C₄ -alkyl radical, R⁸ is a C₁ -C₄ -alkyl radical, or the two radicals are a C₂ -C₆ -alkylene radical which links the two oxygen atoms to form a cyclic acetal and is optionally branched or may carry one or two carboxyl groups, cyclohexyl or phenyl radicals.
 9. A substituted chromen-6-one derivative of the formula VI as claimed in claim 8, where the substituents have the following meanings:R² CH₃, 4,8,12-trimethyltridecyl or 4,8,12-trimethyl-3,7,11-tridecatrienyl, R⁴, R⁵ and R⁶ independently of one another hydrogen or CH₃ and X CN, COOH, COOCH₃, COO--CH₂ --CH₂ --OH, COO--CH₂ --CH₂ --Cl, COO--CH₂ --CH₂ --N(CH₃)₂, CHO, CH₂ OH, CH₂ OCH₃ or CH(OCH₃)₂ or one of the following structural elements X₁ -X₇. ##STR277##10.
 10. A process for preparing substituted chromen-6-one derivatives of the general formula VI as claimed in claim 8, which comprises reacting substituted 5-oxotetrahydropyrans of the general formula IV with substituted vinyl ketones of the general formula V ##STR278##
 11. A process as claimed in claim 10, wherein the substituted 5-oxotetrahydropyrans of the general formula IV are reacted with secondary amines of the formula VIII

    HN(R.sup.9).sub.2                                          VIII

where R⁹ is a C₁ -C₄ -alkyl or phenyl radical, or the two R⁹ radicals represent a C₂ -C₆ -alkylene or C₂ -C₆ -alkoxyalkylene radical bridge to form a cyclic amine,to give the corresponding enamines of the formula IX, ##STR279## the enamines of the formula IX are reacted with the substituted vinyl ketones of the general formula V ##STR280## to give the corresponding keto enamines of the formula X ##STR281## the keto enamines of the formula X are converted by addition of an acid into the corresponding diketone compounds of the formula XI ##STR282## and the diketones of the formula XI are converted by addition of a base into the substituted chromen-6-one derivatives of the general formula VI. 